General
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• Chronic systemic inflammatory disorder affecting synovial lining of joints, bursae and tendon sheaths; also skin, blood vessels, heart, lungs, muscles (Davidson College)
• Produces nonsuppurative proliferative synovitis, may progress to destruction of articular cartilage and joint ankylosis

Epidemiology
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• 1% of adults, 75% are women, peaks at ages 10-29 years; also menopausal women

Sites
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• Small bones of hand affected first (MCP, PIP joints of hands and feet), then wrist, elbow, knee

Pathophysiology
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• Triggered by exposure of immunogenetically susceptible host to arthitogenic microbial antigen; autoimmune reaction then occurs with T helper activation and release of inflammatory mediators and cytokines that destroys joints; circulating immune complexes deposit in cartilage, activate complement, cause cartilage damage
• Parvovirus B19 may be important in pathogenesis (Mod Pathol 2003;16:811)

 

Pathogenesis

Clinical features
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• Clinical course: variable; malaise, fatigue, musculoskeletal pain, then joint involvement; joints are warm, swollen, painful, stiff in morning; 10% have acute onset of severe symptoms, but usually joint involvement occurs over months to years; most damage occurs in first 5 years, joints are unstable with minimal range of motion; 50% have spinal involvement
• Reduces life expectancy by 3-7 years, death due to amyloidosis, vasculitis, GI bleeds from NSAIDs, infections from steroids

Diagnosis
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• Morning stiffness, arthritis in 3+ joint areas, arthritis in hand joints, symmetric arthritis, rheumatoid nodules, rheumatoid factor, typical radiographic changes

Laboratory
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• 80% have IgM autoantibodies to Fc portion of IgG (rheumatoid factor), which is not sensitive or specific; synovial fluid has increased neutrophils (particularly in acute stage), increased protein, low mucin
• Other antibodies include antikeratin antibody (specific, not sensitive), antiperinuclear factor, anti-rheumatoid arthritis associated nuclear antigen (RANA)

Radiology
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• Xray: joint effusions, juxta-articular osteopenia, erosions and narrowing of joint space; destruction of tendons, ligaments and joint capsules produce radial deviation of wrist, ulnar deviation of digits, swan neck finger abnormalities

Radiology images
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Bony lesion

MRI of bony lesion

Case reports
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• 30 year old woman with 7 year history of pain in lumbosacral area and 1 year history of pain in joints of both hands (Chin Med J (Engl) 2011;124:3430)
• 49 year old woman with chief complaint of restricted mouth opening without pain, lasting approximately 4 months (Braz Dent J 2012;23:779)
• 52 year old woman had pain in the right wrist joint for 6 months (Case of the Week #308)
• 72 year old woman with 6 month history of progressive painful swelling of wrists (Int J Surg Case Rep 2011;2:208)
• Woman with pain and edema in second, third and fourth proximal interphalangeal (PIP) joints of hands and wrists (Rev Bras Reumatol 2012;52:648)

Treatment
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• Nonsteroidal anti-inflammatory drugs (NSAIDs); immunosuppressive drugs; joint replacement (synovitis tends to lessen), synovectomy (inflamed synovium may recur and disease may continue to progress)

Clinical images
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Yellowish discharge of altered synovial fluid

Gross description
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• Joints have edematous, thick, hyperplastic synovium, covered by delicate and bulbous fronds
• Osteophytes and new bone formation are not prominent

Gross images
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Swollen and erythematous finger

Knee joint

Micro description
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• Dense perivascular inflammatory infiltrate of T lymphocytes, plasma cells (often with eosinophilic cytoplasmic inclusions called Russell bodies), macrophages; inflammation extends to subchondral bone (relatively specific for rheumatoid arthritis)
• Proliferative synovitis with synovial cell hyperplasia and hypertrophy
• Lymphoplasmacytic infiltrate with variable germinal centers, necrobiotic nodules and fibrosis
• Increased vascularity with hemosiderin deposition
• Organizing fibrin floating in joint space as rice bodies
• Neutrophils present on synovial surface; osteoclasts present in bone forming cysts
• Erosions, osteoporosis; pannus formation (synovium, synovial stroma with inflammatory cells, granulomatous tissue, fibroblasts), progressing to fibrous ankylosis (bridges joints), then ossifying to form bony ankylosis
• Minimal evidence of repair (proliferative cartilage, sclerotic bone or osteophytes)
• Weichselbaum's lacunae: enlarged chondrocyte lacunae within articular cartilage due to dead chondrocytes
• Skin: rheumatoid nodules in 25%, usually those with severe disease in skin subject to pressure (ulnar forearm, elbows, occiput, lumbosacral area); also present in viscera; firm, nontender, with central fibrinoid necrosis surrounded by palisading epithelioid histiocytes, lymphocytes, plasma cells; obliterative endarteritis in vasa nervorum and digital arteries causes ulcers, neuropathy, gangrene
• Blood vessels: small to medium size vessels in vital organs (not kidney) affected by severe erosive disease; rheumatoid nodules present, high titers of rheumatoid factor

Micro images
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Chronic inflammation, plasma cells, lymphocytes

 

Lymphoid follicles

 

Amorphous, pink, necrotic material

Pannus

Rheumatoid nodule

     

Virtual slides
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Rheumatoid nodule

Cytology description
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• May have inflammatory exudate with neutrophils, suggesting an infectious arthritis

Molecular / cytogenetics description
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• More than 20 genetic risk factors
• HLA-DR4, DR1 (65%); PADI4 (Immunogenetics 2011;63:459)
• T-cell antigen receptor motif Q(K/R)RA in 75%
• IL2 signalling pathway involved in T cell activation and proliferation (Curr Opin Rheumatol 2010;22:109)

Molecular / cytogenetics images
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HLA-DR4 molecule

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